Synthesis of chiral 1,2,4-triaminobutanes

Abstract

( S)-5-(Azidomethyl)-2-pyrrolidone, obtained by the Mitsunobu reaction, was reduced to ( S)-5-(aminomethyl)-2-pyrrolidone which was hydrolysed to ( S)-4,5-diaminovaleric acid. The acid, after acylation with i-butyl or with (1 R, 3 R, 4 S)-menthyl chloroformate, underwent a Curtius reaction yielding the corresponding ( S)-1,2-dialkoxycarbonyl-1,2,4-triaminobutane. Alternatively, ( S)-5-(aminomethyl)-2-pyrrolidone was subjected to exhaustive t-butoxycarbonylation followed by ring-cleavage with ammonia to give ( S)- N 4, N 5, N 5-triboc-4,5-diaminovaleramide and was converted by a Hofmann rearrangement to ( S)- N 1, N 2-di- t-butoxy carbonyl-4-methoxycarbonyl-1,2,4-triaminobutane.